rs4774370

Variant names:

• chr15-60601232-T-C
• rs4774370
• NM_134261.3:c.197-69381A>G

Your query was ambiguous. Multiple possible variants found:

• chr15-60601232-T-C
• chr15-60601232-T-G

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_134261.3(RORA):​c.197-69381A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.149 in 152,234 control chromosomes in the GnomAD database, including 1,940 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.15 (1940 hom., cov: 33)
• Consequence: RORA NM_134261.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.41
• Publications: 5 publications found

Genes affected

RORA (HGNC:10258): (RAR related orphan receptor A) The protein encoded by this gene is a member of the NR1 subfamily of nuclear hormone receptors. It can bind as a monomer or as a homodimer to hormone response elements upstream of several genes to enhance the expression of those genes. The encoded protein has been shown to interact with NM23-2, a nucleoside diphosphate kinase involved in organogenesis and differentiation, as well as with NM23-1, the product of a tumor metastasis suppressor candidate gene. Also, it has been shown to aid in the transcriptional regulation of some genes involved in circadian rhythm. Four transcript variants encoding different isoforms have been described for this gene. [provided by RefSeq, Feb 2014]

RORA-AS1 (HGNC:51410): (RORA antisense RNA 1)

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.26).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.283 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RORA	NM_134261.3	c.197-69381A>G		intron_variant	Intron 2 of 10	ENST00000335670.11	NP_599023.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RORA	ENST00000335670.11	c.197-69381A>G		intron_variant	Intron 2 of 10	1	NM_134261.3	ENSP00000335087.6

Frequencies

GnomAD3 genomes AF: 0.149 AC: 22675 AN: 152114 Hom.: 1946 Cov.: 33

Gnomad AFR AF: 0.0529

Gnomad AMI AF: 0.160

Gnomad AMR AF: 0.167

Gnomad ASJ AF: 0.171

Gnomad EAS AF: 0.295

Gnomad SAS AF: 0.153

Gnomad FIN AF: 0.201

Gnomad MID AF: 0.193

Gnomad NFE AF: 0.182

Gnomad OTH AF: 0.174

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.149 AC: 22669 AN: 152234 Hom.: 1940 Cov.: 33 AF XY: 0.154 AC XY: 11427 AN XY: 74436

African (AFR) AF: 0.0530 AC: 2203 AN: 41564

American (AMR) AF: 0.167 AC: 2554 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.171 AC: 593 AN: 3472

East Asian (EAS) AF: 0.295 AC: 1531 AN: 5190

South Asian (SAS) AF: 0.152 AC: 735 AN: 4826

European-Finnish (FIN) AF: 0.201 AC: 2129 AN: 10592

Middle Eastern (MID) AF: 0.201 AC: 59 AN: 294

European-Non Finnish (NFE) AF: 0.182 AC: 12355 AN: 67978

Other (OTH) AF: 0.173 AC: 364 AN: 2110

Alfa AF: 0.170 Hom.: 1726

Bravo AF: 0.144

Asia WGS AF: 0.204 AC: 707 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.26
CADD	Benign	18
DANN	Benign	0.83
PhyloP100		1.4
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs4774370; hg19: chr15-60893431;